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Abstract <p>The synthesis of ketopeptides is garnering significant interest due to their potential in pharmaceutical and health applications. This study introduces an efficient method for synthesizing a novel ketopeptide, 2-amino-6-[(3-hydroxy-1-oxobutyl) amino] hexanoic acid, known as BHB-L, from lysine and methyl-3-hydroxybutyrate (MHB) through an amidation reaction. Conducted under mild conditions (100 °C for 12 hours), this process achieved a lysine conversion rate of 92.5% and resulted in a BHB-L purity of 94.8%. The synthesized BHB-L demonstrated substantial thermal stability and was capable of releasing 3-hydroxybutyric acid (BHB) effectively in simulated human gastrointestinal environments. This research not only provides a feasible pathway for producing BHB-derived ketopeptides but also highlights their potential utility in medical and health-related fields.</p> Graphical abstract <p> A novel ketopeptide is first time prepared from lysine and methyl-3-hydroxybutyrate through amidation reaction, which can release 3-hydroxybutyric acid in simulated human gastrointestinal environments.</p>

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Innovative synthesis of ketopeptide from lysine and methyl-3-hydroxybutyrate

  • 期刊论文

  • 发表日期：

    2025年8月27日

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  • Jiawei Cao,
  • Jinxia Fu,
  • Jianhao Ke,
  • Jiahui Cheng,
  • Hongyi Ren,
  • Xuejing Wang,
  • Zhe Wang,
  • Jiaqi Li,
  • Ruiting Ma,
  • Zijin Xu,
  • Gang Zhang,
  • Shimin Kang

摘要

Abstract

The synthesis of ketopeptides is garnering significant interest due to their potential in pharmaceutical and health applications. This study introduces an efficient method for synthesizing a novel ketopeptide, 2-amino-6-[(3-hydroxy-1-oxobutyl) amino] hexanoic acid, known as BHB-L, from lysine and methyl-3-hydroxybutyrate (MHB) through an amidation reaction. Conducted under mild conditions (100 °C for 12 hours), this process achieved a lysine conversion rate of 92.5% and resulted in a BHB-L purity of 94.8%. The synthesized BHB-L demonstrated substantial thermal stability and was capable of releasing 3-hydroxybutyric acid (BHB) effectively in simulated human gastrointestinal environments. This research not only provides a feasible pathway for producing BHB-derived ketopeptides but also highlights their potential utility in medical and health-related fields.

Graphical abstract

A novel ketopeptide is first time prepared from lysine and methyl-3-hydroxybutyrate through amidation reaction, which can release 3-hydroxybutyric acid in simulated human gastrointestinal environments.